Microbiologically active quaternary ammonium compounds



United States Patent C 3,320,263 MICROBIOLOGICALLY ACTIVE QUATERNARY AMMONIUM COMPOUNDS Reginald L. Wakeman, Philadelphia, Pa, and Joseph F.

Coates, Washington, D.C., assignors, by mesne assignments, to Miilmaster Onyx Corporation, New York, N.Y., a corporation of Delaware No Drawing. Filed Mar. 17, 1964, Ser. No. 352,659 6 Claims. (Cl. 260-286) The object of this invention is the preparation of relatively water-insoluble, bacteriologically active compounds obtained by the reaction of water-soluble quaternary ammonium compounds with water-solbu-le acetylenic alcohol-containing compounds.

The compounds of this invention correspond to the following formula:

where R and R are aliphatic or alicyclic branched or straight chain hydrocarbon radicals containing from about 1 to about 8 carbon atoms, or together comprise an alicyclic hydrocarbon radical, R is H or (|)Zi R2 and Z and Z are either H or a bacteriologically active quaternary ammonium cation, at least one of which is said quaternary ammonium cation.

The ,acetylenic alcohols and glycols which are used in this invention may be prepared by the reaction of acetlyene with one or two moles of a ketone. They are available, for example, under the general trade name Surfy- 1101 from the Air Reduction Chemical & Carbide Co.

Typical example of these acetylenic alcohol-containing products are: Ethyl octynol, ethynyl cyclohexanol, di methyl cyclohexynol, 2,4,7,9 tetramethyl decyl 4,7 diol and the like. Ethyl octynol is 4 ethyl-1 octyne-3 01, or:

Typical examples of the quaternary ammonium compounds which may be used in this invention are the alkyl trirnethyl ammonium chlorides, alkyl-benzyl trimethyl ammonium chlorides, alkyl dimethyl-benzyl ammonium chlorides, alkyl dimethyl menaphthyl ammonium chlorides, alkyl dimethyl substituted-benzyl ammonium chlorides in which the benzyl radical is substituted with one or more side chains containing from 1 to 5 carbon atoms such, for example, as methyl, dimethyl, ethyl and the like and in which the carbon atoms may all be in the same or different side chains or in which the benzyl radical bears one, two or more halogen atoms such as chlorine or bromine, alkyl pyridinium chlorides, alkyl isoquinolinium chlorides and bromides, alkyl lower-alkyl pyrrolidinium chlorides, alkyl lower-alkyl morpholinium chlorides in all of which the alkyl group may have from 8 to 22 carbon atoms and the lower alkyl group may have from 1 to 5 carbon atoms and alkyl phenoxy ethoxy ethyl dimethyl-benzyl ammonium chloride in which the alkyl radical may be iso-octyl or nonyl and in which the benzyl radical may, of desired, be substituted by a methyl radical. Various other analogs of these quaternaries may also be employed such, for example, as cetyl dimethyl ethyl ammonium bromide or oleyl dimethyl ethyl ammonium bromide.

In general, the quaternary ammonium compounds useful in this invention are the higher alkyl quaternary ammonium hydroxides, halides (chlorides and bromides), sulfates, methosulfates and the like possessing the following formula;

where R is an alkyl or alkaralkyl radical containing from 8 to 22 carbon atoms or an alkyl phenoxy ethyl radical in which R is an alkyl radical containing from 8 to 9 carbon atoms and in which the phenyl radical may be substituted by a methyl group; R and R" are methyl or ethyl radicals or members of a heterocyclic ring system such as pyridine, isoquinoline, pyrrolidine and morpholine; R is a methyl radical or a benzyl group or a substituted-benzyl group such, for example, as a monochlorobenzyl radical or a dichlorobenzyl radical or mixture thereof or a methyl benzyl, dimethyl benzyl, ethyl benzyl, diethyl benzyl, isopropyl benzyl, tertiary butyl benzyl, isoamyl benzyl or another benzyl radical containing from 1 to 5 carbon atoms as side chains, either as a single side chain or a multiplicity of side chains including mixtures thereof or a menaphthyl group or hydrogenated menaphthyl group. When R and R are members of a morpholine or pyrrolidine ring, R is a methyl, ethyl, propyl or butyl group. When R and R are members of an unsaturated heterocyclic ring such a pyridine or isoquinoline, R is the same radical as R". X in the above formula corresponds to a halide radical such as chloride, bromide or iodide or to any other water-soluble anion such as methosulfate.

The compounds of this invention may be prepared by mixing aqueous solutions of the quaternary ammonium salts or hydroxides with an aqueous solution of the acid in question or any of its water-soluble salts.

After thorough mixing, the organic product layer is separated from the aqueous layer (as with a separatory funnel) since two distinct phases are formed. Separation may be facilitated by the addition of an organic solvent immiscible with water. The product layer may be washed with water to remove any residual lay-product salt or unreacted materials. The solvent, if any, may be evaporated and the product air or vacuum dried to a paste, wax, oil or solid.

It is not necessary to use an aqueous medium. Any solvent or solvent mixture in which the starting materials are soluble will be satisfactory. Non-aqueous solvents facilitate the separation of by-product inorganic salt and reduce the need for vacuum drying to get an anhydrous product. When a non-aqueous medium is employed, it is usually necessary to add a small amount of water to facilitate ionic reaction.

The product may be used, if desired, without drying since any entrapped water is irrelevant to the microbiological activity of the compounds. In other applications, removal of water may be essential for reasons not related to biological activity.

An alternative method for the preparation of compounds especially applicable to the treatment of fabric, ropes, net, woven and non-woven fabric and reticulated or convoluted materials, involves a two-step process. In the first step, the material is passed through a bath containing the anionic moiety. Excess solution is removed by methods well known to those skilled in the art.

The treated material is then passed through a second bath wherein the concentration of quaternary ammonium compound is such that the material pickup will result in an equivalent amount of quaternary ammonium compound reacting with the anionic moiety, depositing the product in the most intimate way on the surface and in the interstices, convolutions and reticulations of the material.

The method of adjustment of solution concentration to achieve the required pickup is well known to those skilled in the art. The order of treatment may be reversed without affecting the biological activity or durability of the product on the material. The products of this invention may be formulated as water dispersions by dissolving them in a water-miscible organic solvent such as acetone or methanol and diluting with water or by dissolving them in emulsifiable oils such, for example, as sulfonated castor oil or pine oil and diluting with water. In preparing aqueous dispersions, emulsifying agents such, for example, as ethylene oxide condensates of alkyl phenols may be used with or without organic solvents.

It is surprising that the compounds of this invention exhibit high microbiological activity despite their relative insolubility in water. Because of their unusual combination of physical and microbiological properties, they can be used to impart laundry-resistant anti-microbial characteristics to textiles. They can also be used as the active agent in antimildew finishes for textiles which are resistant to leaching with water.

Although the compounds have low water solubility, they are compatible with various organic solvents, plasticizers and high molecular weight compounds. Consequently, they may be incorporated as anti-microbial agents in synethetic resins and plastics. The compounds are compatible with natural and synthetic rubber latices. Therefore, they may be used to prepare bacteriostatic films and molded objects deposited from such latices.

The compounds can be incorporated into cutting and grinding fluids without precipitation. well with non-ionic and anionic surface active agents. In such compositions they retain their micnobiological activity.

It will be understood that the properties of the products described herein will vary depending upon the nature of the cationic quaternary ammonium compound used in their preparation as well as the anionic compound reacted therewith.

The chemical, physical and biological properties of the products of our invention make them especially appropriate for the following applications when suitably incorporated in active amounts in an appropriate vehicle, binder, medium or substrate:

(1) Mildewproofing fabric, canvas, ropes, textiles, awnings, sails, tenting and other woven and non-woven reticulated materials.

(2) Paint mildewstats.

(3) Jet plane fuel additive to control growth of microorganisms.

(4) Odor preservative agents for clothes and shoes.

(5) Mildew retardant and odor suppressant for shoes and other leather products.

(6) Topical antiseptics.

(7) Antidandrufi agents.

(8) Disinfection agents for hair and gut of man and beast.

(9) Bacteriostatic furniture dressing.

(10) Surface finishes for stone, plaster, tile, cement, brick and other inorganic building materials to retard growth of microorganisms, fungi, mold and algae.

(11) Wool preservative.

(12) Plant and tree spray to combat fungi.

(l3) Antimyootic :agents for soap wrappers.

( 14) Self-sanitizing brushes.

(15) Mildewproofing agent in and on plastic and film.

(16) Mildewproofing of cellulosics, cardboard, fibreboard, paper and cordage.

Also, they blend 17) Contact biostat for application to film, waxes and cloth to preserve cheese, meats and vegetables and other food products.

(18) Algal inhibition, especially on surfaces and in solution where low foaming is desirable.

(19) Paper pulp slime control.

(20) Sanitizing agent for rug, carpet, curtains.

(21) Egg preservation.

(22) Adhesive preservation.

(23) Preservation of latex paints.

(24) Preservation of metal-working compounds.

(25) Additives for soap and for both anionic and nonionic detergents in liquid, bar, powder, bead, solution and other forms to impart bacteriostatic and fungistatic properties thereto.

The microbiological activity of our compounds has been evaluated for microbiological stasis by the Standard Tube Dilution test, the technique for which is common knowledge to those skilled in the art. A Difco Bacto CSMA Broth #0826 was used in the study. This test is used to determine the lowest concentration of microbi ologically active compounds which will inhibit the growth of the organism in question. For a Wide range of applications, the inhibition of growth rather than outright kill is satisfactory.

Briefly put, the Tube Dilution test consists in placing 9 cc. of the CSMA Broth in a test tube which is then sterilized in an autoclave. One cc. solution of the microbiologically active compound at an appropriate concentration is added to the test tube which is then inoculated with 0.1 cc. of a twenty-four hour old culture of the organism under study. The test tube is then incubated at 37 C. for forty-eight hours and observed for bacterial growth.

The same procedure is followed for fungi. In such tests, however, the tubes are incubated for fourteen days at a temperature suitable for optimum fungal growth, usually 25 C.

The invention is illustrated by, but not restricted to, the following examples:

Example I In a 500 cc. separatory funnel were placed grams of a 10% solution of the sodium salt of ethyl octynol in 50:50 isopropanol-water and grams of a 10% aqueous solution of alkyl dimethyl ethyl-benzyl ammonium chloride (ETC-471, Onyx Chemical Corp.; alkyl distribution C12 C14 C16 C18 Th6 funnel Was well shaken and benzene added to facilitate layer separation. The organic product layer was separated and dried first on a steam bath and finally in a vacuum oven to give 20 grams (100% yield) of a yellow paste, alkyl dimethyl ethyl-benzyl ammonium ethyl octynolate.

Example 11 Using the technique of Example I, equimolar amounts of sodium ethyl octynolate and alkyl dimethyl benzyl ammonium chloride (ETC-824, Onyx Chemical Corp.; alkyl distribution C 60%, C 30%, C 5%, C 5%) were reacted in aqueous solution and the product separated and dried. An 89% yield of a yellow paste, alkyl dimethyl benzyl ammonium ethyl octynolate, was obtained.

Example 111 Using the technique of Example I, equimolar amounts of sodium ethyl octylnolate and lauryl isoquinolinium bromide (Isothan Q75, Onyx Chemical Corp.) were reacted in aqueous solution and the product separated and dried. A 100% yield of a dark red paste, lauryl isoquinolinium ethyl octynolate, was obtained.

Example IV The products from Example IIII were tested in the Standard Tube Dilution test described above against Staphylococcus aureus (S.a.), Salmonella typhosa (S.t.)

and Aspergillus niger (A.n.). Results of these tests are shown in Table I.

TAB LE I Reciprocal of Static Dilution of Product vs. Sodium Ethyl Octynol Reaction Product With- S.a. S.t. A.n.

Alkyl Dimethyl Ethyl-B enzyl Ammonium Chloride 10 10; Alkyl Dimethyl Benzyl Ammonium Chloride. 1G 10 10 Lauryl Isoquinolim'um Bromide 10 10 10 Example V The product from Example III was tested at a dilution of 121000 against Pityrosporum ovale according to the Use Dilution test of the Association of Ofiicial Agricultural Chemists (Ofiicial Methods of Analysis, 1960, page 65 et seq.). Results showed that ten out of ten tubes were negative.

Example VI A 25% by weight solution of each of the compounds of Examples I-III was prepared in ethylene glycol monobutyl ether. Four parts of each of these solutions were added to 96 parts of a latex acrylic type paint and Well mixed. Each of the emulsions thus prepared was inoculated with a culture of Pullalaria pullulans and incubated at 25 C. and 90% relative humidity for three weeks. At the end of this time, no fungus growth was visible in the latex.

Example VII Using the technique of Example I, equimolar amounts of solutions of the mono sodium salt of 2,4,7,9 tetnamethyl 5 decyn 4,7 diol and lauryl isoquinolinium bromide were reacted and the product separated and dried. The dark red mono lauryl isoquinolinium 2,4,7,9 tetramethyl 5 decyndiolate was obtained in essentially theoretical yield.

Example VII In a similar manner, equimolar amounts of solutions of ethynyl cyclohexanol and lauryl isoquinolinium bromide were reacted and the product separated and dried. Ap-

proximately theoretical amounts of lauryl isoquinolinium ethynyl cyclohexanolate were recovered.

We claim: 1. The compound having the structure:

o-z Ra-CEC-(:]- h

wherein R and R are selected from the group of alkyl and cycloalkyl branched and straight chain group having from 1 to 8 carbon atoms, and alkylene groups wherein R and R together comprise a cycloalkyl group; R represents a member of the group consisting of hydrogen and UNITED STATES PATENTS 1/1952 CrOXall et a1 260-30 OTHER REFERENCES Fieser et al.: Advanced Organic Chemistry, Reinhold, 1961, p. 219.

Schwartz et al.: Surface Active Agents and Detergents, vol. II, Interscience, 1958, page 22 and 230 relied upon.

ALEX MAZEL, Primary Examiner. HENRY R. JILES, Examiner.

DONALD G. DAUS, Assistant Examiner. 

1. THE COMPOUND HAVING THE STRUCTURE:
 6. LAURYL ISOQUINOLINIUM 2,4,7,9 TETRAMETHYL 5 DECYNDIOLATE. 